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Am J Physiol Endocrinol Metab 283: E138-E145, 2002. First published March 27, 2002; doi:10.1152/ajpendo.00426.2001
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Vol. 283, Issue 1, E138-E145, July 2002

Role of cytokines and testosterone in regulating lean body mass and resting energy expenditure in HIV-infected men

Ronenn Roubenoff1,2, Steven Grinspoon3, Paul R. Skolnik1, Eric Tchetgen1, Leslie Abad2, Donna Spiegelman1,4, Tamsin Knox1, and Sherwood Gorbach1

1 Department of Community Health and Department of Medicine and 2 Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center, Tufts University, Boston 02111; 3 Division of Endocrinology, Massachusetts General Hospital, Boston 02114; and 4 Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115

Although catastrophic weight loss is no longer common in HIV-infected men, we hypothesized that a more gradual process of cachexia [loss of lean body mass (LBM) without severe weight loss, often accompanied by elevated resting energy expenditure (REE)] is still common and is driven by excessive production of the catabolic cytokines tumor necrosis factor-alpha (TNF-alpha ) and interleukin-1beta (IL-1beta ). We performed a longitudinal analysis of an ongoing cohort study of nutritional status in 172 men with HIV infection. LBM loss of >1 kg occurred in 35% of the cohort, and LBM loss of >5% occurred in 12.2% over 8 mo of observation, but classical wasting (loss of approx 10% of weight) was rare (2%). Both TNF-alpha (-150 g LBM · ng-1 · ml-1, P < 0.02) and IL-1beta production (-130 g LBM · ng-1 · ml-1, P < 0.01) by peripheral blood mononuclear cells predicted loss of LBM. A rise in REE of >200 kcal/day was found in 17.7% of the subjects regardless of weight change. IL-1beta (+9 kcal/day per ng/ml, P < 0.002) and TNF-alpha (+10 kcal/day per ng/ml, P < 0.02) production predicted Delta REE. Serum free testosterone was inversely associated with TNF-alpha production and was not an independent predictor of either Delta LBM or Delta REE after adjustment for cytokine production. Even though weight loss was rare in this cohort of patients treated with highly active antiretroviral therapy, loss of LBM was common and was driven by catabolic cytokines and not by inadequate dietary intake or hypogonadism.




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